Behavioral control of the respiratory system involves voluntary acts such as breathholding and reflexive acts such as sneezing, coughing, and swallowing. All of these acts are stat e-dependent and generally occur only in wakefulness. Many are important for defense of the airways. For example, in addition to its role in alimentation, swallowing is the final act in clearance of mucous from the airways. Impaired swallowing, coughing and sneezing lead to aspiration and/or irritation of the airways, which are incompatible with life. Behavioral control of the respiratory system is poorly understood. Our studies of normal animals trained to perform a behavioral respiratory response show that control in this case occurs within the automatic system of the brainstem. When inspiration is stopped behaviorally, inspiratory neurons in the brainstem are inactivated. This inactivation is not caused by cells that inhibit inspiratory neurons during normal breathing. It may be caused instead by cells that receive both respiratory and nonrespiratory inputs (low n2 cells). These cells may act as an interface that mediates behavioral and reflexive control of the respiratory system. The studies of this proposal will test this theory. We will determine if low n2 cells that are activated during behavioral inhibition of inspiration are activated also by stimuli that cause reflexive apneas and the defensive respiratory responses of sneezing, coughing, and swallowing. To this end, brainstem respiratory neuronal activity and respiratory muscle activity will be recorded during defensive respiratory responses elicited by nasal, pharyngeal, and tracheobronchial stimulation in wakefulness and NREM and REM sleep in intact adult cats. These studies will address the neural mechanisms of apnea, the coordination of the respiratory system during sneezing, coughing and swallowing, and the effect of sleep on defensive respiratory responses.